Improving life for cancer patients through transformative drugs

Transcription

1 Investor call Q Improving life for cancer patients through transformative drugs 1 April 27, 2017 July 2018

2 Important notice You must read the following before continuing. The following applies to this document and the information provided in this presentation by Medivir AB (publ) (the Company ) or any person on behalf of the Company and any other material distributed or statements made in connection with such presentation (the Information ), and you are therefore advised to carefully read the statements below before reading, accessing or making any other use of the Information. In accessing the Information, you agree to be bound by the following terms and conditions. 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4 Improving life for cancer patients through transformative drugs Using world-class scientific expertise to bring new therapies to cancer patients Clinical pipeline composed of projects with multibillion dollar sales potential as well as orphan cancer drug candidates Strong commercial focus delivered more than 20 global partnerships and 2 products from idea to market Basic facts Headquarters in Huddinge, Sweden 77 employees, 43 with PhDs Listed on the Nasdaq Stockholm, ticker: MVIR Current market capitalization: SEK 800m (~USD 90m) 1 Website: 4 1) As of July 2, Stock price 33,00 SEK

5 Discover Leveraging scientific expertise to build pipeline in oncology Protease inhibitors Protease Targets Birinapant Protease Targets Nucleoside prodrugs Remetinostat Birinapant Protease Targets MIV-818 Leukotide 5 Adapted from: The Hallmarks of Cancer: The Next Generation. Hanahan and Weinberg, Cell (2011), 144,

6 Cancer Develop Oncology drug development in areas of high unmet need Strong and balanced development pipeline based around areas of scientific expertise and focused on cancer Clinical phase Project, Mechanism Disease area Preclinical Phase I Phase II Phase III Market Remetinostat Topical HDAC inhibitor Birinapant SMAC mimetic MIV-818, Nucleotide DNA polymerase inhibitor MIV-711 Cathepsin K inhibitor Early-stage cutaneous T-cell lymphoma Solid tumors (combo with Keytruda ) Hepatocellular carcinoma Osteoarthritis ~$1b US only Blockbuster Orphan US/EU Significant Asia Blockbuster 6 Protease related Nucleot(s)ide related

7 Industrial Academic Partner Collaborations enhance the value of programs Product/Project Platform Link Partners Status Medivir Interests Zoviduo /Xerclear (labial herpes) acyclovir + hydrocortisone Nucleoside analogue Marketed Royalties from sales Approval milestones for additional OTC switches 7 MIV-802 (HCV) Nucleotide NS5B polymerase inhibitor Nucleotide Phase I ready Development milestones Royalties from sales

8 Competences from discovery through regulatory approvals Management team with extensive experience and proven track record of successful development 8 CHRISTINE LIND, President and CEO EVP, Business Development at Medivir VP, Business Development, LifeCell Corporation Biotech and pharma strategic advisory and capital raising at Merrill Lynch & Co. and GKM & Co. B. Sc. Finance and Info Systems, NYU and MBA, Columbia Business School RICHARD BETHELL, Chief Scientific Officer 28 years drug discovery and development in oncology and infectious disease VP, Biology/DMPK (Boehringer Ingelheim (Canada)) VP, Therapeutic Research (Shire) Pfizer and GlaxoSmithKline R&D Doctor of Philosophy (D. Phil.) in chemistry from Oxford University ÅSA HOLMGREN, EVP Strategic Regulatory Affairs Head of Regulatory Affairs at Orexo AB Various large pharmaceutical companies, including 12 years as Senior Global Regulatory Affairs Director at AstraZeneca, and at AstraZeneca in Canada and Japan M. Sc. in Pharmacy, trained Uppsala University Cancer biology, chemistry, intellectual property, DMPK, CMC, toxicology, clinical development, regulatory strategy, business development ERIK BJÖRK, Chief Financial Officer CFO for AstraZeneca Sweden Operations 11 years with Procter & Gamble, in global finance leadership positions in Switzerland, UK and Sweden MSc in Finance and LLM from Lund University CHRISTINA HERDER, EVP Strategic Business Development CEO of Modus Therapeutics Director, Corporate Development at Sobi Project & Portfolio Management at Biovitrum Current member of the boards of PCI Biotech and Idogen Ph. D. in physical chemistry from Royal Institute of Technology and MBA from Stockholm University DANIEL ERIKSSON, Chief Information Officer Various IT roles relating to security, decision support, innovation, and digitalization Most recently, Technical Director for G4S Risk Management PhD Coventry University and BSc in Systems Science, Linköping University 77 employees, 43 with PhDs, 18 nationalities, balanced gender split

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10 MIV-711: ORAL ONCE DAILY CATHEPSIN K INHIBITOR WITH FDA FAST TRACK STATUS FOR OA DISEASE MODIFICATION No existing disease-modifying drug for osteoarthritis Blockbuster revenue opportunity for a disease-modifying osteoarthritis drug Affects >30m adults in the US, and ~240m worldwide Prevalence increasing due to aging population and obesity epidemic Current treatments are insufficient focusing only on symptom relief Disease involves both bone and cartilage Cathepsin K protease involved in the breakdown of collagen in both bone and cartilage Healthy Osteoarthritis Annual US market potential 1 >$6bn 10 Yuan et al. Osteoarthritis and Cartilage (2014), 22, 1077 Sources: Hunter et al, Nat Rev Rheumatol, 2014; Reginster et al, Ann Rheum Dis ) >2M adults in US with moderate osteoarthritis in weight bearing joints at annual treatment cost for a drug that impacts disease progression of 3,000 USD/Year (Losina et al 2014)

11 MIV-711: ORAL ONCE DAILY CATHEPSIN K INHIBITOR WITH FDA FAST TRACK STATUS FOR OA DISEASE MODIFICATION Phase IIa data show unprecedented OA disease modification after 6 months Potential disease-modifying convenient osteoarthritis drug Only cathepsin K inhibitor in development for osteoarthritis Once daily oral administration Strong patent position Expected patent life to ~2034, including extensions US FDA Fast Track designation Granted by FDA October 2017 The finding that MIV-711 slows the degenerative changes on both bone and cartilage in knees affected by OA is an enormously exciting finding 11 Professor Philip Conaghan, Professor of Musculoskeletal Medicine at the University of Leeds, UK, and MIV-711 lead investigator Benefit on both bone and cartilage in Phase IIa study Change in medial femur joint bone area (%) 1% increase 66% reduction (p=0.002) 63% reduction (p=0.004) Placebo 100mg 200mg n=66 n=69 n=69 Change in central medial femur cartilage thickness (µm) (p=0.023) (p=0.125) Placebo 100mg 200mg n=66 n=69 n=69 MIV-711 consistent tendency to improve outcomes across all pain and other patient reported symptoms vs. placebo and sustained with additional 6 months treatment Acceptable safety and tolerability profile 65.6 decrease Abstract 14L

12 MIV-711: ORAL ONCE DAILY CATHEPSIN K INHIBITOR WITH FDA FAST TRACK STATUS FOR OA DISEASE MODIFICATION MIV-711: Building towards partnership Q Q Q Q Q April 2016 Amsterdam, Netherlands Partnering discussions ongoing 12 September 2017 Phase IIa Initial study Screening 200 mg once daily Placebo October 2017 US FDA Fast Track Designation n=82 n= mg once daily n=80 Visits W0 W26 W30 November 2017 Late breaking poster San Diego, USA No significant clinical worsening Significant clinical worsening Phase IIa Extension study 200 mg once daily W0 n= 50 June 2018 Followup Followup W26 W30 Additional joint structure data results expected 3Q 2018

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14 REMETINOSTAT: TOPICAL HDAC INHIBITOR DESIGNED FOR TREATMENT OF EARLY-STAGE CUTANEOUS T-CELL LYMPHOMA CTCL: orphan blood cancer with significant market opportunity US CTCL patients 1 : orphan disease Early stage (IA-IIA) Market Size 2 $900m Early Stage CTCL: Disease background Confined to the skin High 5-year survival rates (~85%) Patients remain at this stage for extended periods and require long-term treatment Significant quality of life issues, especially pruritus (itch) 14 Late stage (IIB-IV) Key unmet need: balance of efficacy and long-term tolerability 1) Leukemia & Lymphoma Society; 2) Early-stage patients at $ per patient year price based on market research and competitive topical treatment pricing. The Medical Letter, Issue 1467, April 27, 2015 and Actelion public information

15 REMETINOSTAT: TOPICAL HDAC INHIBITOR DESIGNED FOR TREATMENT OF EARLY-STAGE CUTANEOUS T-CELL LYMPHOMA Patients & physicians need new treatments for early-stage CTCL Currently approved therapies by disease stage Currently approved early-stage CTCL drugs lack sustained efficacy and/or tolerability and are highly irritating Valchlor/Ledaga is a topical alkylating agent (the active agent in mustard gas) No single treatment for long-term use At this early stage, physicians avoid using systemic drugs, including other HDAC inhibitors, due to the side effect profile Stage IA-IIA Topical corticosteroids 1 st line Local radiation Valchlor/ Ledaga PUVA Electron Beam Therapy UVB Topical retinoid 2) Stage IA-IIA refractory Stage IIB and beyond Systemic agents (incl. systemic HDAC inhibitors) 15 1) Medivir market research; 2) Full approval in USA only

16 Fraction remaining (%) REMETINOSTAT: TOPICAL HDAC INHIBITOR DESIGNED FOR TREATMENT OF EARLY-STAGE CUTANEOUS T-CELL LYMPHOMA Remetinostat potential to meet patients key unmet need Designed to act only where needed HDAC inhibitors 1 approved in late-stage CTCL patients but not in early-stage patients due to systemic toxicities Remetinostat s unique design and topical application provides activity in skin, but rapid degradation in blood Stability of remetinostat Human blood vs. Human skin homogenate As a topical, skin-specific HDAC inhibitor, remetinostat has the potential to be efficacious and have an improved safety profile compared to other available treatments. Time (min.) Youn Kim M.D. Stanford University Medical Center, USA Expected patent life to ~2034 (including extensions) US orphan drug designation 16 1) HDAC inhibitor = histone deacetylase inhibitor

17 REMETINOSTAT: TOPICAL HDAC INHIBITOR DESIGNED FOR TREATMENT OF EARLY-STAGE CUTANEOUS T-CELL LYMPHOMA Addresses key unmet need with positive Phase II data Effect on lesions & reduction of pruritus (itch) Dose 1% 1x/day n=20 0.5% 2x/day n=20 1% 2x/day n=20 Lesion responses 1 20% 25% 40% Patients with clinically significant pruritus 2 8/20 (40%) 6/20 (30%) 10/20 (50%) Pruritus responses 37.5% 50% 80% Highly tolerable with no systemic side effects Even dose distribution of AEs, mostly grade 1 or 2 No HDAC inhibitorassociated systemic adverse events Median time on treatment: 332 days (1% 2x/day dose) M Duvic et al., EORTC Cutaneous Lymphoma Task Force Meeting (2017), Abstract O ) Confirmed responses based on CAILS, the Composite Assessment of Index Lesion Severity 2) Clinically significant pruritus defined at baseline as VAS 30 mm

18 REMETINOSTAT: TOPICAL HDAC INHIBITOR DESIGNED FOR TREATMENT OF EARLY-STAGE CUTANEOUS T-CELL LYMPHOMA Planned Phase III clinical development for early-stage CTCL Q Q H H April 2017 Positive data announced from the phase II study in patients with early-stage CTCL October 2017 London, England May 2018 Orlando, USA Ongoing discussions with the FDA (End of Phase II) to enable Phase III Design 18 The introduction of remetinostat to the market as a novel topical agent for the treatment of CTCL is likely to find broad application and lead to novel combinatorial approaches in CTCL. Pierluigi Porcu, M.D. Jefferson University Hospital, USA One Phase III study expected to be sufficient for NDA Past approvals in CTCL were based on pivotal clinical studies involving 260 patients Focus on treatment-experienced patients where the medical need is high Costs ~$50m (SEK 400m) expected clinical costs to NDA submission over a ~3 year period (incl. Phase III study and third party milestones)

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20 BIRINAPANT: UNIQUELY POTENT MOLECULE AGAINST A NOVEL TARGET IN CANCER Despite immuno-oncology breakthroughs patients have unmet needs Multi-billion dollar market, and growing for immunooncology agents Revenues of PD-1/PD-L1 inhibitors 1) $10bn+ < 1/2 of patients derive meaningful clinical benefit in approved indications 0-5% ORR in other indications such as MSS colorectal cancer Combination regimens to enhance benefit in underserved patients 20 1) Merck (Keytruda), Bristol-Myers Squibb (Opdivo), AstraZeneca (Imfinzi) and Roche (Tecentriq) financial reports, twelve months ended March 31, 2018

21 BIRINAPANT: UNIQUELY POTENT MOLECULE AGAINST A NOVEL TARGET IN CANCER Linking targeted therapy with immuno-oncology Uniquely potent molecule against a novel target Bivalent SMAC (second mitochondrial-derived activator of caspases) mimetic Targeting of ciaps results in dual action on T-cells and tumor cells Strong rationale for use in combinations Synergistic with anti-pd1 and likely other IO pathways Efficacy observed in both hematological and solid tumor models Phase I/II study in combination with Merck s Keytruda underway Blockbuster potential and strong patent position Expected patent life to ~2034, including extensions 21

22 BIRINAPANT: UNIQUELY POTENT MOLECULE AGAINST A NOVEL TARGET IN CANCER Dual action enhances cancer cell death Targeting of ciaps results in dual action on T-cells and tumor cells Enhances pro-apoptotic, and suppresses pro-survival, signaling downstream of TNF-a Augments human T cell responses to physiologically relevant stimuli 1 Tumor cell Birinapant T eff -cell APOPTOSIS Birinapant ciap-1 ciap-1 ciap-1 ACTIVATION SURVIVAL ciap-1 TNFα TNFα 22 1) Dougan et al., J. Exp. Med. (2010) 207:2195 TNFα TNFα TNFα

23 BIRINAPANT: UNIQUELY POTENT MOLECULE AGAINST A NOVEL TARGET IN CANCER Potential to enhance patient response with immune-oncology therapies Strong rationale for combination with Keytruda Birinapant/anti-PD1 mab combo showed enhanced activity in preclinical models 1 compared to either agent alone Phase I/II study underway in collaboration with Development collaboration for the Phase I/II study in solid tumors Keytruda provided at no cost Joint Development Committee to oversee the study, bringing Merck s immuno-oncology expertise Medivir retains full global rights to birinapant and data 1) Solid tumor model: Beug et al., Nature Communications (2017) 8:14278 Multiple myeloma model: Chesi et al., Nature Med. (2016) 22, Cooperation of IAPs and PD-L1 to protect tumor cells: Kearney et al., Cell Death and Diff. (2017), 24,

24 BIRINAPANT: UNIQUELY POTENT MOLECULE AGAINST A NOVEL TARGET IN CANCER Birinapant/Keytruda combination: Phase I/II Study underway Q H H June 2018 Chicago, USA Phase I dose escalation n=24 Birinapant + Keytruda Current stage Phase I: Sequential group dose-escalation to determine the dose-limiting toxicity and recommended Phase II dose, in combination with Keytruda Phase II expansion Birinapant + Keytruda Phase II: Safety and tolerability of the recommended dose of birinapant, in combination with Keytruda in defined disease cohorts: n=ca.80 Follow-up 24 MSS Colorectal cancer Ovarian cancer Cervical cancer Other cancer types exploratory cohort

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26 MIV-818: LIVER-TARGETED NUCLEOTIDE PRODRUG DESIGNED FOR THE TREATMENT OF LIVER CANCERS Liver cancer is 2 nd leading cause of cancer related death worldwide Liver cancer 1 Orphan disease in Western markets, but much more common in Asia One of fastest growing and most deadly cancers in US Genetically heterogeneous leading to limited effect of molecularly targeted therapies Patients with advanced liver cancer in need of new treatments Sorafenib (kinase inhibitor) ~3 month survival benefit Regorafinib (kinase inhibitor) ~3 month survival benefit Nivolumab (PD-1 antagonist) 15-20% ORR Survival benefit yet to be fully defined 1) Howlader et al. (eds). SEER Cancer Statistics Review, , National Cancer Institute. Bethesda, MD, 26

27 MIV-818: LIVER-TARGETED NUCLEOTIDE PRODRUG DESIGNED FOR THE TREATMENT OF LIVER CANCERS Potential to improve efficacy and safety for patients with liver cancers Improve a nucleoside with Medivir prodrug technology Troxacitabine (nucleoside) Active in preclinical cancer models and in clinic Failed in clinic due to systemic doselimiting toxicities Medivir prodrug technology MIV-818 (liver-targeted nucleotide prodrug) Exhanced activity 10x more potent against HCC cell lines than parent troxacitabine Selectivity for cancer Active on HCC cells while sparing non-cancerous hepatocytes Improved delivery to the liver >100- fold relative to systemic exposure of troxacitabine Market exclusivity with full new chemical entity patent protection 27

28 MIV-818: LIVER-TARGETED NUCLEOTIDE PRODRUG DESIGNED FOR THE TREATMENT OF LIVER CANCERS MIV-818: Gearing up for Phase I study start Q Q Q Q Q H 2018 September 2016 Vancouver, Canada February 2017 The Asian Pacific Association for the Study of the Liver (APASL) Shanghai, China February 2017 April 2017 Completed MIV-818 (liver cancer) IND-enabling preclinical studies Washington DC, USA March 2018 April 2018 Chicago, USA Planned start of Phase I study (2H 2018) Geneva, Switzerland Geneva, Switzerland 28

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30 Cash position and shareholder base CASH POSITION Cash and ST investments SEK523m (USD 60m) Q Successful out-licensing: additional cash mid-term Investments in R&D Estimated 1.5 years cash runway THE SHARE Market Cap 1) ~800m SEK (~USD 90m) International Ownership ~30% Top 20 shareholders ~51% 30 1) As of July 2, Stock price SEK. 24,287,818 total Class B shares as reported April 30, 2018.

31 Key milestones throughout the year Track record of delivery Coming events Completed MIV-818 (liver cancer) IND-enabling preclinical studies MIV-818 Geneva, Switzerland March 2018 MIV-818 Chicago, USA April 2018 MIV-711 Remetinostat Orlando, USA May 2018 Birinapant Chicago, USA June 2018 Completed MIV-711 Phase IIa osteoarthritis extension study Completion of the dose escalation portion of the birinapant Phase I/II study in combination with Keytruda (2H 2018) Start of MIV-818 (HCC nuc) Phase I study (2H 2018) Start of Phase III CTCL study remetinostat (2019) Upcoming Financial Reports 2Q interim report (July 25, 2018) 3Q interim report (October 26, 2018) Year end report (February 14, 2019) 31

32 Why Medivir? For more information: Nasdaq Stockholm, ticker: MVIR Track record of delivery 3 new drugs from research into development in 2 years 2 products from idea to market >20 global partnerships, multiple repeat partners Strong pipeline from discovery through clinical stages with upcoming catalysts Competences from discovery through regulatory approvals Near-term opportunities for revenues from partnerships 32